Multi-dye theranostic nanoparticle platform for bioimaging and cancer therapy

Amit K Singh,1,2 Megan A Hahn,2 Luke G Gutwein,3 Michael C Rule,4 Jacquelyn A Knapik,5 Brij M Moudgil,1,2 Stephen R Grobmyer,3 Scott C Brown,2,61Department of Materials Science and Engineering, College of Engineering, 2Particle Engineering Research Center, College of Engineering, 3Division of Surgical Oncology, Department of Surgery, College of Medicine, 4Cell and Tissue Analysis Core, McKnight Brain Institute, 5Department of Pathology, College of Medicine, University of Florida, Gainesville, FL, USA; 6DuPont Central Research and Development, Corporate Center for Analytical Science, Wilmington, DE, USABackground: Theranostic nanomaterials composed of fluorescent and photothermal agents can both image and provide a method of disease treatment in clinical oncology. For in vivo use, the near-infrared (NIR) window has been the focus of the majority of studies, because of greater light penetration due to lower absorption and scatter of biological components. Therefore, having both fluorescent and photothermal agents with optical properties in the NIR provides the best chance of improved theranostic capabilities utilizing nanotechnology.Methods: We developed nonplasmonic multi-dye theranostic silica nanoparticles (MDT-NPs), combining NIR fluorescence visualization and photothermal therapy within a single nanoconstruct comprised of molecular components. A modified NIR fluorescent heptamethine cyanine dye was covalently incorporated into a mesoporous silica matrix and a hydrophobic metallo-naphthalocyanine dye with large molar absorptivity was loaded into the pores of these fluorescent particles. The imaging and therapeutic capabilities of these nanoparticles were demonstrated in vivo using a direct tumor injection model.Results: The fluorescent nanoparticles are bright probes (300-fold enhancement in quantum yield versus free dye) that have a large Stokes shift (>110 nm). Incorporation of the naphthalocyanine dye and exposure to NIR laser excitation results in a temperature increase of the surrounding environment of the MDT-NPs. Tumors injected with these NPs are easily visible with NIR imaging and produce significantly elevated levels of tumor necrosis (95%) upon photothermal ablation compared with controls, as evaluated by bioluminescence and histological analysis.Conclusion: MDT-NPs are novel, multifunctional nanomaterials that have optical properties dependent upon the unique incorporation of NIR fluorescent and NIR photothermal dyes within a mesoporous silica platform.Keywords: bioluminescence, in vivo imaging, mesoporous silica nanoparticles, NIR fluorescence, photothermal ablation, theranosti

Polyhydroxy Fullerenes (Fullerols or Fullerenols): Beneficial Effects on Growth and Lifespan in Diverse Biological Models

Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols), have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF) and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF). We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF

Role of Powder Properties and Flowability in Polymer Selective Laser Sintering—A Review

Polymer selective laser sintering (SLS) is an additive manufacturing technology that involves the melting of a selected area of particles on the powder bed. A 3D component is then printed using layer-by-layer sintering of the powder bed. SLS is considered one of the most promising technologies applicable to a variety of applications, particularly for manufacturing customized design products with high geometric complexity, such as patient-specific designed implants, surgical tools. Currently, only a small number of polymers are available that are suitable for SLS due to the complex multiple physical phenomena involved. Therefore, it is critical to develop new materials in order to fully realize the potential of SLS technology for manufacturing value-added customized products. For a given material, the quality of powder spreading in SLS plays a key role in printing performance and is a precondition for new material development. The aim of this review is to (1) present flowability characterization methods suitable for SLS, (2) examine the influence of powder properties and flowability on laser–material interaction and the quality of the final part, and (3) discuss the methods adopted in the literature to improve the quality of powder spreading

Fluorescent nanoparticle probes for cancer imaging

Optical imaging technique has strong potential for sensitive cancer diagnosis, particularly at the early stage of cancer development. This is a sensitive, non-invasive, non-ionizing (clinically safe) and relatively inexpensive technique. Cancer imaging with optical technique however greatly relies upon the use of sensitive and stable optical probes. Unlike the traditional organic fluorescent probes, fluorescent nanoparticle probes such as dye-doped nanoparticles and quantum dots (Qdots) are bright and photostable. Fluorescent nanoparticle probes are shown to be very effective for sensitive cancer imaging with greater success in the cellular level. However, cancer imaging in an in vivo setup has been recently realized. There are several challenges in developing fluorescent nanoparticle probes for in vivo cancer imaging applications. In this review, we will discuss various aspects of nanoparticle design, synthesis, surface functionalization for bioconjugation and cancer cell targeting. A brief overview of in vivo cancer imaging with Qdots will also be presented